Rapid resolution of GVHD after orthotopic liver transplantation in a patient treated with alefacept

Stotler, Christy; Eghtesad, Bijan; Hsi, Eric D.; Silver, Bernard J.

doi:10.1182/blood-2009-02-207431

Cited by 29 publications

(21 citation statements)

References 10 publications

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“…This patients' condition was deteriorating despite high-dose steroids, filgrastim support, and rabbit antithymocyte globulin, therefore off-label use of the immunosuppressant alefacept was recommended. After the initial 30 mg alefacept dose, the patients' blood counts improved and remained stable 13 months later [24]. This patient had GVHD after OLT confirmed by short tandem repeat (STR) analysis of four samples; a buccal swab (recipient DNA), donor DNA-Allogen labs, peripheral blood and T-cell enriched fraction from peripheral blood.…”

Section: Successesmentioning

confidence: 85%

“…Several current studies support alefacept-mediated depletion of CD2 hi T cells in patients during allogeneic hematopoietic stem cell transplant, liver or kidney [22][23][24][25]. All patients developed post-transplant graft-versushost disease (GVHD) but GVHD resolved even after termination of alefacept therapy and patients did not require immunosuppressive drugs [22].…”

Section: Successesmentioning

confidence: 94%

“…Alefacept has not only been used for the treatment of psoriasis but was successfully repurposed for other diseases that involved T cell activation such as type I diabetes (T1D) [20,21], preconditioning in allogeneic hematopoietic stem cell transplantation (HSCT) of pediatric patients with life-threatening nonmalignant diseases [22], kidney and liver transplantation [23][24][25], atopic dermatitis (AD) [26,27],…”

Section: Repurposing Of Alefacept In Different Human Diseases: Succesmentioning

confidence: 99%

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Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

Zaidi¹,

Meng²

2016

Immunother Open Acc

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Current anti-retroviral treatment (ART) for HIV is effective in maintaining HIV at undetectable levels. However, cessation of ART results in immediate and brisk rebound of viremia to high levels. This rebound is driven by an HIV reservoir mainly enriched in memory CD4 + T cells. In order to provide any form of functional HIV Cure, elimination of this viral reservoir has become the focus of current HIV cure strategies. Alefacept was initially developed for the treatment of chronic plaque psoriasis. Alefacept is a chimeric fusion protein consisting of the CD2-binding portion of human leukocyte function antigen-3 (LFA3) linked to the Fc region of human IgG1 (LFA3-Fc). Alefacept was designed to inhibit memory T cell activation that contributes to the chronic autoimmune disease psoriasis by blocking the CD2 coreceptor. However, it was found to deplete memory T cells that express high levels of CD2 via NK cellmediated antibody dependent cell cytotoxicity (ADCC) in vivo. Phase II and phase III clinical trials of alefacept with psoriasis patients demonstrated promising results and an excellent safety profile. Subsequently, alefacept has been successfully repurposed for other memory T cell-mediated autoimmune diseases including skin diseases other than psoriasis, organ transplantation and type I diabetes (T1D). Herein, we review our specific strategy to repurpose the FDA approved biologic alefacept to decrease and hopefully someday eliminate the HIV reservoir, for which CD2 hi memory CD4 + T cells are a significant contributor.

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Section: Successesmentioning

confidence: 85%

Section: Successesmentioning

confidence: 94%

Section: Repurposing Of Alefacept In Different Human Diseases: Succesmentioning

confidence: 99%

See 1 more Smart Citation

Can We Repurpose FDA-Approved Alefacept to Diminish the HIV Reservoir?

Zaidi¹,

Meng²

2016

Immunother Open Acc

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“…Case reports have described successful therapies for GVHD related to liver transplant, including infl iximab, 15 etarnercept, 16 and alefacept. 17 Ultimately, because of the rarity of the disease, no evidence-based guidelines for therapies exist. However, it is possible that earlier diagnosis of SOT-GVHD may allow improved treatment response.…”

Section: Discussionmentioning

confidence: 99%

Solid-Organ Graft-Versus-Host Disease After Liver Transplant: A Case Report

Auerbach

Schott

2016

Critical Care Nurse

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Solid-organ transplant graft-versus-host disease (SOT-GVHD) is a rare complication of organ transplant that is associated with high mortality. The initial signs and symptoms are vague, so this disease is easily confused with other posttransplant complications. A case of SOT-GVHD occurred after orthotopic liver transplant for liver failure due to hepatitis C in a patient in a Veterans Affairs intensive care unit. The patient had dehydration, acute kidney injuries, rashes, diarrhea, and pancytopenia. Results of skin biopsy, bone marrow biopsy, and cytogenetic studies were consistent with SOT-GVHD. Despite supportive care including antibiotics, antiviral and antifungal therapy, high-dose steroids, antithymoglobulin and neupogen, the patient died of overwhelming sepsis. Owing to the rarity of SOT-GVHD, no evidence-based guidelines or recommendations for treatment exist. Treatment includes high-dose corticosteroids and antibiotic, antifungal, and antiviral prophylaxis. Treatment of liver transplant–related GVHD with anti–tumor necrosis factor a agents has been successful.

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“…Some authors proposed a reduction or even withdrawal of immunosuppression in order to restore the recipient's immune system to fight the immune attack of the donor (7). Some others immunosuppression increase with different patterns: increased basal immunosuppression, adding methyl-prednisolone boluses (2,4), or the use of antilymphocyte therapy such as anti-thymocyte globulin, antilymphocyte globulin, OKT3, daclizumab or basiliximab, guest cell infusion, rapamycin (3,(8)(9)(10)(11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%